| 1. |
- Backmark, Anna, 1979, et al.
(författare)
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Affinity tags can reduce merohedral twinning of membrane protein crystals
- 2008
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Ingår i: Acta Crystallographica. Section D: Biological Crystallography. - 1399-0047 .- 0907-4449. ; D64, s. 1183-1186
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Tidskriftsartikel (refereegranskat)abstract
- This work presents a comparison of the crystal packing of three eukaryotic membrane proteins: human aquaporin 1, human aquaporin 5 and a spinach plasma membrane aquaporin. All were purified from expression constructs both with and without affinity tags. With the exception of tagged aquaporin 1, all constructs yielded crystals. Two significant effects of the affinity tags were observed: crystals containing a tag typically diffracted to lower resolution than those from constructs encoding the protein sequence alone and constructs without a tag frequently produced crystals that suffered from merohedral twinning. Twinning is a challenging crystallographic problem that can seriously hinder solution of the structure. Thus, for integral membrane proteins, the addition of an affinity tag may help to disrupt the approximate symmetry of the protein and thereby reduce or avoid merohedral twinning.
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| 2. |
- Lindgren, Lena, et al.
(författare)
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Regions of importance for interaction of puumala virus nucleocapsid subunits
- 2006
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Ingår i: Virus genes. - : Springer Science and Business Media LLC. - 0920-8569 .- 1572-994X. ; 33:2, s. 169-174
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Tidskriftsartikel (refereegranskat)abstract
- Puumala virus (PUUV) is a hantavirus that causes a mild form of hemorrhagic fever with renal syndrome in northern and central Europe, and in large parts of Russia. The nucleocapsid (N) protein encoded by hantaviruses plays an important role in the life-cycle of these viruses, and one important function for the N-protein is to oligomerize, surround and protect the viral RNAs. We have identified amino- and carboxy-terminal regions involved in PUUV N-N interactions, which comprise amino acids 100-120 and 330-405. Our findings strengthen the hypothesis that the amino-terminus of the N-protein of hantaviruses holds a more regulatory function regarding N-N interactions, while conserved residues in the carboxy-terminal region, F335 together with F336 and W392, in concert with Y388 and/or F400 seems to play a more critical role in the PUUV N-N formation. This study provides evidence that the amino-terminal regions involved in the N-N interaction of Puumala virus are similar to those reported for Seoul virus (SEOV) and to some extent Hantaan virus (HTNV), even though the identity between PUUV N and SEOV/HTNV N is markedly lower than between PUUV N and Tula virus (TULV) N or Sin Nombre virus (SNV) N.
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| 3. |
- Dreilich, Martin, et al.
(författare)
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Telomerase activity is not a key determinant of sensitivity to standard cytotoxic drugs in human esophageal carcinoma cell lines
- 2006
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Ingår i: Anti-Cancer Drugs. - 0959-4973 .- 1473-5741. ; 17:5, s. 503-509
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Tidskriftsartikel (refereegranskat)abstract
- The aim of the present study was to investigate if basal telomerase activity levels may predict sensitivity to cytotoxic drugs in a panel of human esophageal carcinoma cell lines. The TRAPeze telomerase detection assay was used to investigate telomerase activity in the cell lines. Cytotoxic drug sensitivity for 20 standard cytotoxic agents was assessed using the fluorometric microculture cytotoxicity assay (FMCA). Telomerase activity was detected in all cell lines with a broad range of activity levels. Drug sensitivity also varied considerably between the cell lines. Except for a P value towards a correlation between mitoxantrone and telomerase activity (P=0.054), no statistically significant correlation was found between telomerase activity levels and sensitivity to investigated drugs, including key drugs such as cisplatin (P=0.9), 5-fluorouracil (P=0.8) and doxorubicin (P=0.54). We therefore conclude that basal telomerase activity level is not a key determinant of sensitivity to standard cytotoxic drugs in esophageal carcinoma cell lines.
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| 4. |
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| 5. |
- Lindkvist, Anna, 1976-
(författare)
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Activity and Regulation of Telomerase in Malignant Cells
- 2006
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- An important step in tumorgenesis is the acquisition of cellular immortality. Tumor cells accomplish this by activating the enzyme telomerase, and thereby avoiding replicative senescence. The aim of this thesis was to study the activity and regulation of telomerase in a panel of malignant cell types.We found that TGF-β1 (transforming growth factor-β1) mediated differential effects on telomerase activity in five ATC (anaplastic thyroid carcinoma) cell lines. Cells that harbored a p53 mutation responded by up-regulation of telomerase activity after TGF-β1 treatment, whereas cell lines displaying wt p53 responded by down-regulation of telomerase activity. Thus, these results indicate a possible connection between p53 genotype and telomerase response to TGF-β1 treatment. Furthermore, the decreased telomerase activity appeared to be due to transcriptional repression of the hTERT promoter and the increased activity possibly involved hTERT activation via phosphorylation. We have previously shown that IFNs (interferons) sensitize MM (multiple myeloma) cells to Fas-mediated apoptosis. In the present investigation both IFN-α and IFN-γ down regulated telomerase activity in the MM cell line U-266-1970. The mechanism underlying the reduction of telomerase activity by IFN was shown to be transcriptional repression of the hTERT gene. We suggest that one potential mechanism whereby IFN sensitize MM cells to Fas-mediated apoptosis is by repressing hTERT activity at the transcriptional level. In the next study we demonstrated that basal telomerase activity is not a key determinant of sensitivity to cytotoxic drugs in ESCC (esophageal squamous cell carcinoma) cell lines. Furthermore, we observed no correlation between c-Myc amplification, p53 mutations and high telomerase activity levels in these cell lines. Finally, neuroblastoma cell lines were shown to up-regulate telomerase activity in response to hypoxic exposure and the main regulatory mechanism was not mediated by increased hTERT mRNA expression. This finding might constitute an adaptive stress response of tumor cells exposed to hypoxia.
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| 6. |
- Lindkvist, Anna, et al.
(författare)
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Differential effects of TGF-beta1 on telomerase activity in thyroid carcinoma cells
- 2005
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Ingår i: Biochemical and Biophysical Research Communications - BBRC. - : Elsevier BV. - 0006-291X .- 1090-2104. ; 338:3, s. 1625-1633
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Tidskriftsartikel (refereegranskat)abstract
- The aim of the present study was to investigate the effect of transforming growth factor-beta1 (TGF-beta1) on telomerase activity in a panel of human anaplastic thyroid carcinoma (ATC) cell lines. Addition of TGF-beta1 decreased the telomerase activity in HTh 74 and KTC-1 cells, while in C 643 and HTh 7 an increased activity was observed. The decreased telomerase activity appeared to be due to transcriptional repression of the hTERT promoter. Addition of a PI-3 kinase inhibitor (LY294002) abrogated the stimulatory effect of TGF-beta1 on the telomerase activity, indicating the possible involvement of hTERT activation via phosphorylation. Furthermore, the MEK-inhibitor U0126 had similar effects suggesting dual regulatory mechanisms. Interestingly, the cell lines differed genetically in that ATC cell lines responding with increased telomerase activity harbored a p53 mutation. In conclusion, TGF-beta1 exerts opposing effects on telomerase activity in ATC cell lines, possibly reflecting deregulation of TGF-beta1 signaling in a more malignant genotype.
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| 7. |
- Lindkvist, Anna, 1976-
(författare)
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En lappmissionärs dagböcker berättar
- 2008
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Ingår i: Västerbotten. - Umeå : Västerbottens läns hembygdsförening. - 0346-4938. ; :1, s. 26-36
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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| 8. |
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| 9. |
- Lindkvist, Anna, 1976-
(författare)
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Jorden åt folket : nationalföreningen mot emigrationen 1907-1925.
- 2007
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- This thesis deals with the National Society Against Emigration (Sw.Nationalföreningen mot emigrationen) – referred to as the NE – and its radical right-wing leader Adrian Molin. Th e NE was founded in 1907 in order to stem the tide of emigration from Sweden and facilitate re-immigration by providing jobs and accomodation. Its many bureaus served as employment offi ces, land distribution centres and own-your-own-home companies, mainly aimed at creating smallholdings for Swedish working-class families. The purpose of the study is to investigate the organization, concept and practise of the internal colonization of rural Sweden between 1907 and 1925. By following both the successes and setbacks of the NE during the first decades of the twentieth century, ideas and opportunities circulating in Swedish society in a time of wide-ranging ideological and material change are discussed. Questions in focus include why a society to prevent emigration from Sweden emerged at that particular time; the function it served for both society and the state; the form internal colonization actually took and how it was conducted in comparison with other governmental and private agricultural reforms; and the attitude of the NE toward modernization in general. Theoretically the dissertation takes its point of departure in theories on nation-building and internal colonization (i.e., the establishment of small-scale farming and the cultivation of new land within the national borders), corporatism and attitudes toward modernization. The ideological analysis has been inspired by political scientist Michael Freeden´s theory of the construction of political ideologies via political concepts, as well as an analysis of the view of social categories such as gender, class and ethnicity. The source material is comprised of magazines, newspaper articles, letters and books and offi cial parliamentary publications. The practise of internal colonization has been studied with the aid of preserved accounts of the NE’s small-scale farming colonies, real estate documents, company reports, correspondance and further press materials. The surge of anti-emigration attitudes is explained as a powerful reaction arising at the turn of the century due to the economic upswing in Swedish industry and the social transformations which followed in the 1890s, when the country was seen as a nation with a promising future. That Adrian Molin founded the NE in 1907 is viewed as a consequence of his nationalistic thought. Together with political scientist Prof. Rudolf Kjellén, Molin was one of the country´s foremost advocates of an integrative nationalism. The NE was led by an elite of middle- and upper-class men involved in politics, industry and voluntary associations. Female members and representatives of the lower social classes were mostly absent. In general the NE neglected women in both speeches and plans, being preoccupied with ideas concerning the cultivation of middle-class Swedish men. The NE became a co-actor in a corporative colonization eff ort sanctioned by government financing during the 1910s. In 1920 the NE’s projects were condemned as hierarchical and undemocratic in comparison with other own-home organizations. Many other own-home companies were built on a cooperative foundation, while the NE was run by a national, regional, and local political and financial elite. Suspicions were raised about the raison d´être of the society. The state withdrew its subsidies and loans, and the NE lost it close connections with the government. Though conservative and reactionary in social issues, the NE cannot be characterized as critical of civilization or economic modernization of the country. Its programme intended to aid in the development of both agriculture and industry. The creation of more smallholdings would help bridge the problematic transition between two systems, from agrarian to industrial society.
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| 10. |
- Lindkvist, Anna, et al.
(författare)
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Konflikt och konsensus i skogen : intensivodling av skog ur ett humanistiskt och samhällsvetenskapligt perspektiv. Faktaunderlag till utredning om Möjligheter till intensivodling av skog
- 2009
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- Den första delstudien, ”Skogslandskapet som arena”, syftar till att ge en bakgrund till dagens skogsbruk i Sverige och att sätta in skogspolitiken i ett idé- och miljöhistoriskt sammanhang. Sammantaget handlar undersökningen om hur skogen har brukats och hur detta brukande har motiverats, institutionaliserats, reglerats och ifrågasatts under de senaste århundradena. Den består av två delar. Den första delen inleds med en historik som tar upp maktförhållandena i skogen och hur skogen har nyttjats genom tiderna. Därefter följer en redogörelse över skogsbrukets och skogsvårdslagens förändring över tid fram till att miljörörelsen, rennäringen, kulturminnesvården och andra ”allmänna intressen” som värnar om skogen tar plats i skogsvårdslagen. I den andra delen diskuteras ett urval konflikter som uppkommit i anslutning till skogen och skogsbruket, främst med tyngdpunkt på 1970- och 1980-talen: debatten om plantering av skog i öppna landskap, kalhyggesdebatten, reaktionerna vid inplantering av främmande trädslag, debatten om bruket av bekämpningsmedel samt visionen om att utveckla och nyttja genmodifierade träd. Flera av dessa konflikter kan rimligen åter aktualiseras vid ett intensifierat skogsbruk av det slag som utredningen behandlar.Den andra delstudien, ”Attityder och värderingar”, undersöker privatpersoners och skogsägares inställningar till den svenska skogen i allmänhet och till intensivodling av skog i synnerhet. Privatpersoner betraktar vanligen skogen som en rekreationsresurs, medan skogsägare håller skogens traditionella, ekonomiska värden närmare hjärtat. När attityder mot skogen väl förändras beror det ofta på generationsväxlingar, ökat miljömedvetande och urbaniseringstrender. Sveriges stora demografiska och kulturella skillnader har även bidragit till att skogen idag uppfattas olika i olika delar av landet. Samtidigt som vi bor längre bort från skogen än tidigare ökar vår efterfrågan på dess sociala värden, vilket innebär att ungefär hälften av våra skogsbesök numera sker i tätortsnära skog, som främst är förknippad med rekreation och vila. Skogens ekonomiska värden är emellertid fortfarande viktiga, inte minst när det gäller skogens roll som framtida energikälla. Intervjuade skogsägare har visat sig vara förhållandevis positiva till intensivodling av skog, samtidigt som det av miljömässiga och ekonomiska skäl finns ett starkt motstånd mot att öka användningen av gödsel. Privatpersoner som intervjuats anser i regel att intensivodlade områden begränsar naturupplevelsen, skadar miljön och missgynnar mångfalden. Fördelar som ökad möjlighet att utvinna alternativa energibränslen och ökade exportmöjligheter för svensk industri har emellertid också nämnts.Den tredje delstudien, ”Potentiella synergier och målkonflikter”, relaterar intensivodling av skog dels till de av riksdagen fastställda miljömålen dels till eventuella intressemotsättningar som kan uppstå till följd av ett förändrat nyttjande av jordbruksmark. De målkonflikter som identifieras, främst mellan miljömålen ’Begränsad klimatpåverkan’ och ’Ett rikt växt- och djurliv’, kan inte enbart lösas på teknisk väg utan kräver någon form av politisk avvägning. För att ansvariga myndigheter ska kunna göra en sådan avvägning krävs dock att det utarbetas någon form av politisk prioriteringsordning som kan vägleda myndigheterna i det arbetet. När det gäller eventuella intressemotsättningar som kan uppstå till följd av intensivodling framgår det av intervjuer med olika intresseorganisationer att många konflikter sannolikt kan undvikas om synpunkter från olika intressen beaktas i samband med planering av förändrat marknyttjande.
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